The present invention relates generally to vascular implants and, more particularly, to a synthetic or artificial prosthetic valve device for implantation in a blood vein. In another aspect, the present invention relates to a method for making the same. In yet another aspect, the present invention relates to a method for implanting the venous valve device of the present invention. In still another aspect, the present invention relates to a method for the treatment, reversal, and/or prevention of venous insufficiency and its consequences in animals, including humans.
Venous blood flow returns de-oxygenated blood from the distal extremities to the heart via two mechanisms. The first is the perfusion pressure resulting from the arterial blood flow through tissue to the venous circulation system. Where arterial pressure prior to perfusion may be 60 to 200 mm Hg, the resulting venous pressure is typically 10 to 40 mm Hg. The second mechanism is the calf muscle, which, when contracted, compresses the veins (tibial and peroneal) overlying the bone and, through a system of valves, directs blood flow toward the heart. This is the organized flow of blood through a normal, healthy person.
Venous valves, especially those in the upper leg, perform an important function. When a person rises from a seated to a standing position, arterial blood pressure increases instantaneously to insure adequate perfusion to the brain and other critical organs. In the legs and arms, the transit time of this increased arterial pressure is delayed, resulting in a temporary drop in venous pressure. Venous pressure drops as blood flow responds to body position change and gravity, thereby reducing the volume of blood available to the right heart and possibly reducing the flow of oxygenated blood to the brain. In such a case, a person could become light headed, dizzy or experience syncope. It is the function of valves in the iliac, femoral and, to a lesser degree, more distal vein valves to detect these drops in pressure and resulting change of direction of blood flow and to close to prevent blood from pooling in the legs to maintain blood volume in the heart and head. The valves reopen and the system returns to normal forward flow when the reflected arterial pressure again appears in the venous circulation. Compromised valves, however, would allow reverse blood flow and pooling.
Venous insufficiency is caused by compromised vein valves in the leg. Venous insufficiency is recognized in two forms: (1) chronic venous ulcer, and (2) varicose veins. In the United States, chronic venous insufficiency (CVI) associated with skin changes and ulcers effect six to seven million people. Each year, 900,000 new patients are diagnosed with this disorder while 800,000 patients suffer the consequences of active venous ulcers. Health care costs in the United States are estimated at one billion dollars with a loss of 2 million days of productivity. The costs in the western industrial countries exceed those of the United States.
Skin changes and ulcers due to venous insufficiency usually result from valve damage or deep venous occlusion following a bout of DVT. Active venous ulcers are the leading cause of leg ulceration and the long-term healing prognosis, when compared to arterial and diabetic ulcers, is poor. While estimated to be 10 times more common, chronic venous insufficiency has received less attention than arterial insufficiency. CVI is the seventh most debilitating disease in the United States. Principle risk factors associated with venous ulcers include increased age, obesity, male gender, lower extremity trauma, and a history of deep vein thrombosis (DVT).
Varicose veins, the second manifestation of chronic venous insufficiency, occur when walls of the vein lose their elasticity, causing vessel dilation that stretches the valves to incompetence. Varicose veins are estimated to affect 4.2% of the adult western population. It is also estimated that 27% of the United States adult population have some form of detectable lower extremity venous abnormality, primarily varicose veins and telangiectasia. Approximately half of this population has significant varicose veins for which treatment will be sought. Primary risk factors are a history of phlebitis, female gender, and a family history of varicose veins.
Traditional conservative therapy relies primarily on compression hosiery, such as that devised by Jobst in 1950. The goal of this therapy is to reduce symptoms while allowing patients to remain ambulatory and productive. Active venous ulcers are often treated with a combination of topical drug therapy and pressure dressing as first described by Unna in 1896. However, the prognosis of chronic venous ulcers is poor, with only 50% healing within 4 months. In most cases, the ulcer will recur at least once.
Surgical therapy, consisting of high ligation and vein stripping for varicose veins was first described by Trendelenburg in 1891 and was improved by Keller in 1905. This approach generally provides a good cosmetic result with reduction in symptoms. However, procedures that remove the saphenous vein also deprive the patient of the best conduit for cardiac and peripheral arterial reconstruction. This may bring into question the precept of leaving varicose veins alone until they become a problem. Dilated and varicose vessels are not appropriate for use as arterial conduits.
Surgeons, recognizing the value of valve restoration, have devised surgical procedures for selected patients to create, repair, and/or transplant vein valves in an effort to restore “normal” venous blood flow and heal ulcers. Patient selection and the operator are key to the success of these procedures.
Criado et al. [1] provide a good overview of venous disease including venous insufficiency and a rational for current treatment options.
In 1985, Hill et al. [2], described artificial valve prosthesis. In this experiment, Pellethane® urethane elastomer was used to fabricate a valve. A human umbilical cord valve was used for casting a valve in the Pellethane material. The valves were mounted in a stainless steel tube for implant in animal model. The fabricated valve remained patent for from 5 to 8 days. Results suggested more study was necessary to improve long-term durability.
Bemmelen et al. [3] is one of a series of reports that looks at the mechanical operating characteristics of the native human valve. The pressure and velocity measurements documented in the study, as well as the measurement methods used, provide a basic understanding of venous flow dynamics.
One cause of venous insufficiency is the loss of elasticity in the vein wall. In 1993, van Cleef [4] documented the orientation of valves and perforating vessels. The paper refers to an implantable device that, when placed parallel to the valve leaflets, will stretch the leaflets to competency. The percutaneous prosthesis consists of two stems and a leaf spring opening the stems. The device is not a valve replacement, but rather allows flattening of the vessel and, when placed parallel to the valve cusps, allows retightening of the native valve cusps. This understanding is important because an artificial valve may replace the “stretched” valve and it must accommodate the vein lumen enlargement.
In 1988, Taheri et al. [5], fabricated mechanical valves with pyrolyte carbon coated titanium and platinum. The sizes of these bileaflet valves were from 5 to 10 mm in diameter. An annular ring was provided so that a suture could be placed around the implanted device to secure position and orientation in the vessel. This valve was patterned after a bileaflet cardiac valve. This series demonstrated both patency and competency to reverse flow at 16 weeks. Two valves did occlude when they physically migrated to other anatomic locations within the venous system. No anticoagulants were used in this series. The employed valves and others are described in Taheri [6].
In 1995, Taheri et al. [7], published their long-term experience with the bileaflet valve. In this series, nine dogs were implanted with the bileaflet mechanical vein valves for up to two years. Over this period, all valves were rendered functionless because of a dense ingrowth of intimal hyperplasia.
In 1993, DeLaria et al. [8], described their in-vitro experience with a glutaraldehyde-fixed valve and metal mounting system using a venous flow simulator. The report suggests this device performs well to the parameters expected in the venous circulation. This report describes the use of a glutaraldehyde-fixed bovine jugular vein in an animal model. Tissue fixation of this type is common in heart valves. The authors note that valve failures were related to intimal hyperplasia related to tissue ingrowth at the sewing ring.
Transplants of human tissue are often considered the best replacements. In 1997, Reeves et al. [9] investigated the mechanical characteristics of lyophilized human saphenous vein valves in vitro as a potential source of valves for transplantation.
Cryopreserved human aortic valves and valved conduits are routinely used to replace cardiac valves and for cardiac outflow reconstructions. Burkhart et al. [10] describes the result of cryopreserved valved saphenous vein transplantation, specifically, the use of cryopreserved venous valve allografts in greyhounds.
Dalsing et al. [11] investigated the use of cryopreserved venous valve allograft in humans. This follow-up study suggests that the cryopreserved approach is best suited for patients without other options.
Kumins et al. [12] describe free tissue transfer for treatment of large venous ulcers, resulting in transplantation of hundreds of functioning microvenous valves, as a substitute for valveplasty. The devastation of venous ulcers has led many to find a cure without correction of the underlying circulation defects. This paper suggests a cure can be had for between $30,000 and $76,000.
Patented experimental work on prosthetic venous valves is generally focused on two groups: (1) Syde Taheri, who proposes a mechanical valve based on the St. Jude heart valve concept, and (2) the Baxter group whose venous valve is based on glutaraldehyde-fixed heart valve devices. Briefly, Taheri et al. [5, 6, 7] were the first to report a metallic vein replacement valve. This device was effective in the animal model for treating venous insufficiency. At 3 to 8 months, valve patency was demonstrated. In [7], it was reported that over a 2-year period, valve function was compromised by intimal hyperplasia. These results may be better than they appear, since the tissue ingrowth may have been controlled by an attachment method designed to limit intimal ingrowth.
DeLaria et al. [8], above, (Baxter sponsored) describe in vitro mechanical experience with a glutaraldehyde-fixed bovine jugular vein. Quijano et al. [13, 14], disclose stents and other implantation devices for use with prosthetic valve grafts, such as preserved valve-containing vein segments. A drawback of the disclosed prosthesis is that it includes a mechanical device to connect and restrain vessels and to enclose a glutaraldehyde valve.
With the exception of Hill et al. [2], most attempts to fabricate venous valves were based on the design and materials proven appropriate for heart valves. Heart valves open and close 60 to 150 times per minute with pressures of up to 250 mm Hg. On the other hand, venous valves typically remain open with minimal forward flow and close with flow reversal. Reverse venous flow may develop intermittent pressures of 150 mm Hg.
Therefore, there exists a need in the art for an improved artificial venous valvular prosthetic device that overcomes the above-referenced problems and others.